WO2007026883A1 - COMPOSÉ D'INSERTION AVEC POLYMÈRE INSÉRÉ DANS UN a-1,4-GLYCANE ET SON PROCÉDÉ DE PRODUCTION - Google Patents

COMPOSÉ D'INSERTION AVEC POLYMÈRE INSÉRÉ DANS UN a-1,4-GLYCANE ET SON PROCÉDÉ DE PRODUCTION Download PDF

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WO2007026883A1
WO2007026883A1 PCT/JP2006/317359 JP2006317359W WO2007026883A1 WO 2007026883 A1 WO2007026883 A1 WO 2007026883A1 JP 2006317359 W JP2006317359 W JP 2006317359W WO 2007026883 A1 WO2007026883 A1 WO 2007026883A1
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Prior art keywords
amylose
glucan
hydroxyl group
polymer
group
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PCT/JP2006/317359
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English (en)
Japanese (ja)
Inventor
Mitsuru Akashi
Toshiyuki Kida
Takashi Minabe
Takeshi Takaha
Junichi Takahara
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Osaka University
Ezaki Glico Co., Ltd.
Sanwa Cornstarch Co., Ltd.
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Application filed by Osaka University, Ezaki Glico Co., Ltd., Sanwa Cornstarch Co., Ltd. filed Critical Osaka University
Publication of WO2007026883A1 publication Critical patent/WO2007026883A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L71/00—Compositions of polyethers obtained by reactions forming an ether link in the main chain; Compositions of derivatives of such polymers
    • C08L71/02—Polyalkylene oxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B33/00—Preparation of derivatives of amylose
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
    • C08B37/0015—Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes

Definitions

  • the present invention relates to a polymer inclusion complex of ⁇ -1,4-glucan and a method for producing the same.
  • Molecular recognition capability is a very important function in developing various functional materials. As a means for molecular recognition, the ability to form inclusions is attracting attention. Inclusion is a phenomenon in which a molecule with a cavity called a host molecule takes a guest substance into the cavity. A substance in which a guest substance is incorporated into a host molecule is called an inclusion compound.
  • Examples of host molecules include amylose-1,4 glucan).
  • Amylose is a polymer in which many glucoses are linearly bound, has a helical molecular structure, and encloses a guest substance in a hollow interior.
  • Non-Patent Document 1 There are many reports on complexes of amylose and low molecular weight compounds (for example, Non-Patent Document 1).
  • Kadokawa et al. Use poly (tetramethylene oxide) or poly ( ⁇ -force prolatatone) as a template to wrap around the polymer chain.
  • An example is known in which an inclusion complex of amylose and a polymer is obtained by enzymatic polymerization of glucose 1-phosphate to amylose (Non-Patent Document 2).
  • Non-Patent Document 2 There is no known example in which a polymer substance is directly encapsulated in the hollow interior. Due to the strong helical structure based on the intramolecular hydrogen bond of amylose, it is considered difficult to incorporate the polymer into the amylose guest substance.
  • Non-Patent Document 1 Starch Science No. 34 No. 1 p. 49-57 (1987)
  • Non-Patent Document 2 J. Kadokawa et al. Chem. Eur. J. 2002, 8, 3321.
  • the present invention has been made in view of the above circumstances, and a novel amylose inclusion complex obtained by directly including a polymer substance in the hollow interior of an amylose host molecule and the production thereof It aims to provide a method.
  • the present invention provides an inclusion complex comprising an ⁇ -1,4-glucan host molecule partially modified with a hydroxyl group and a polymeric guest substance, and a method for producing the same.
  • ⁇ 1, 4 glucan is a saccharide having D glucose as a constituent unit in the present specification, and having at least two saccharide units linked only by a 4-darcoside bond.
  • ⁇ -1,4-glucan is a linear molecule.
  • ⁇ -1,4 glucan is also called linear glucan.
  • the number of sugar units contained in one molecule of ⁇ -1,4 glucan is called the degree of polymerization.
  • degree of polymerization refers to the weight average degree of polymerization unless otherwise specified. In the case of ⁇ -1,4-glucan, the weight average degree of polymerization is calculated by dividing the weight average molecular weight by 162.
  • the "host molecule” refers to a compound having a molecular structure that forms a void, such as ⁇ 1,4 glucan-cyclodextrin.
  • inclusion refers to a state in which a host molecule incorporates a guest substance through a specific bond whose structure can be uniquely determined, and the bond is indefinite, such as aggregation or adsorption to the surface. Cannot be represented by the structure of! /, Excluding non-specific states.
  • inclusion complex refers to a substance in which a host molecule and a guest substance are integrated by inclusion, and an aggregate thereof. Excludes non-specific agglomerates, mere mixed 'dispersions, and those covered by a film such as a capsule.
  • ⁇ -1, 4 glucan is a genolecan phosphorylase (a- glucan phosphorylase EC 2.
  • ⁇ -1,4 glucan using glucan phosphorylase is a method in which glucan phosphorylase is allowed to act on glucose-1-phosphate (G-1-—) as a substrate in the presence of maltooligosaccharide. (GP method).
  • sucrose phosphorylase and glucan phosphorylase are allowed to act simultaneously on a substrate using SP (GP-GP).
  • SP GP-GP
  • This method has the advantage that inexpensive sucrose can be used as a raw material because glucan phosphorylase acts on G-1-P generated by the action of sucrose phosphorylase to synthesize 1,4 glucan.
  • the ⁇ 1,4-glucan obtained by any of the above methods is a completely linear molecule without any branched structure of natural starch, and therefore has no branched structure. Easy to spiral structure.
  • the molecular weight can be arbitrarily controlled by the reaction conditions, and the molecular weight distribution is very narrow.
  • the molecular weight (weight average molecular weight) of ⁇ 1,4-glucan synthesized using glucan phosphorylase can be arbitrarily controlled within the range of about 5,000 to several millions.
  • the molecular weight distribution (MwZMn) is 1.25 or less, which is much narrower than that of natural amylose.
  • those having a weight average molecular weight of 10,000 to several hundred thousand, preferably about 20,000 to 70,000 are suitable.
  • those having a weight average degree of polymerization of about 20 to 400, preferably about 40 to 140 are suitable.
  • 4-glucan is sometimes simply referred to as “amylose”.
  • Natural amylose is contained in starch in about 20% and can be prepared by amylose selective precipitation using butanol. However, this natural amylose has various problems when actually used as a host molecule. Since natural amylose has a branched structure that is not completely a linear structure, it cannot exhibit an excellent inclusion ability. Natural amylose is a mixture of amylose having a wide degree of polymerization, and amylose having a specific degree of polymerization cannot be obtained.
  • Enzymatic amylose is an ⁇ -1,4-glucan synthesized using an enzyme and has a completely straight chain structure without a branched structure. Is possible. In the present invention, it is preferable to use enzyme-synthesized amylose.
  • the hydroxyl group is partially modified.
  • the modification of the hydroxyl group is synonymous with the substitution of the hydrogen atom of the hydroxyl group with a substituent.
  • the position of the hydroxyl group to be modified is 2, 3, or 6 position, preferably 2, 3 position. 6th It is known that the amylose helical structure is disrupted when the hydroxyl group is modified (Hui et al. Makromol. Chem. 1988, 189, 1287.). It is done.
  • the substituent is an alkyl group such as a methyl group or an ethyl group, preferably a methyl group, a carboxymethyl group, or an acetyl group.
  • Partial means that all of the hydroxyl groups contained in ⁇ -1,4-glucan are not substituted with substituents, preferably hydroxyl groups at the 2, 3, 6 positions, more preferably It is substituted with 3 to 20 mol% of the hydroxyl group at the 2nd and 3rd positions. If the substitution ratio is lower than 3 mol%, it is difficult to form inclusion complex with the polymer guest substance due to the strong helical structure based on the intramolecular hydrogen bond of amylose, and the ratio is 20%. When it is larger than mol%, the intramolecular hydrogen bond of amylose is weakened, it becomes difficult to form a helical structure, and it becomes difficult to form an inclusion compound with a polymeric guest substance.
  • the method for producing an ⁇ -1,4-glucan host molecule partially modified with a hydroxyl group is as follows.
  • a halogenated alkyl dialkyl sulfate or phosphoric acid is used in a solvent or in the absence of a solvent under alkaline conditions. This can be done by the action of an alkylating agent such as trimethyl.
  • alkylating agent such as trimethyl.
  • alkyl halides include methyl iodide, acetyl iodide, methyl bromide, acetyl bromide, methyl chloride, ethyl chloride and the like.
  • dialkyl sulfuric acid include dimethyl sulfuric acid and jetyl sulfuric acid.
  • Modification with a carboxymethyl group can be carried out by allowing monochloroacetic acid to act under alkaline conditions in a solvent or in the absence of a solvent.
  • Modification with a acetyl group can be carried out by reacting an enzymatically synthesized amylose with a acetyl chloride reaction reagent such as butyl acetate, acetic anhydride, or isopropanol acetate in a solvent or without a solvent.
  • a acetyl chloride reaction reagent such as butyl acetate, acetic anhydride, or isopropanol acetate in a solvent or without a solvent.
  • the hydroxyl groups at the 2- and 3-positions of ⁇ -1,4-glucan are selectively modified with alkyl groups.
  • ⁇ -1,4-glucan is reacted with triphenylmethyl chloride in the presence of pyridine in a solvent to selectively select the trityl group at the 6-position hydroxyl group of 4-glucan.
  • Protect with. A 1,4-glucan with a hydroxyl group at the 6-position protected with a trityl group is added with NaH in a solvent, and an alkylating agent such as a halogenated alkyl is allowed to act on it.
  • the alkyl halide include methyl iodide and iodinated chill.
  • the trityl group protecting the hydroxyl group at the 6-position is deprotected with an acid such as hydrochloric acid to obtain ⁇ -1,4-glucan in which the hydroxyl groups at the 2,3-position are selectively modified.
  • Modification with the acetyl group includes dissolving hi-1,4-glucan in which the 6-position hydroxyl group is protected with a trityl group in dimethyl sulfoxide, adding pyridine, and then allowing acetic anhydride to act. It can be carried out.
  • the ratio of the degree of substitution of the substituent can be adjusted by adjusting the addition amount of the alkylating agent or the addition amount of NaH. it can.
  • Carboxymethyl candy can be obtained by adjusting the amount of acetic acid added to black mouth acetic acid.
  • it in the case of acetylene cake, it can be carried out by controlling the amount of acetylation reagent added and the reaction time.
  • the desired degree of substitution can also be obtained by subjecting ⁇ - 1,4-glucan having a high degree of substitution to an alkali catalyst such as sodium hydroxide or an alkali catalyst such as sodium methoxide for deacetylation.
  • the degree of substitution is calculated by the integration ratio in NMR measurement.
  • the ⁇ -1,4-glucan is synthesized by trimethylsilylating all the hydrogen atoms of the hydroxyl group remaining in the ⁇ -1,4-glucan with partially modified hydroxyl groups.
  • the 1 H-NMR measurement can be performed to determine the integral specific force.
  • the polymer as the guest substance is selected from polyether (I), polyester (II), and polyamide (III) forces represented by the following structural formula.
  • n represents an integer of 5 to 50, more preferably 10 to 40.
  • R 2 In formula (II), R represents a hydrogen atom, a methyl group or an ethyl group, preferably a hydrogen atom;
  • n represents an integer of 3 to 5, preferably 4 to 5; n is 5 to: LOOO, preferably 5 to 100
  • R represents a hydrogen atom, a methyl group or an ethyl group, preferably a hydrogen atom.
  • M represents an integer of 1 to 5, preferably 3 to 5; n is 10 to 400, preferably 10 to 40
  • the inclusion complex of the present invention can be obtained by dissolving an ⁇ -1,4-glucan host molecule partially modified with a hydroxyl group and a polymer guest substance in the same solvent and mixing them. .
  • the solvent used in the present invention is a solvent that can dissolve both the host molecule and the guest molecule, and preferably a solvent that can be dissolved at room temperature.
  • a solvent for example, water or a mixed solvent of water and an organic solvent compatible with water is used.
  • organic solvents that are compatible with water include dimethyl sulfoxide (DMSO), ethanol, methanol, acetone, acetonitrile, isopropanol, tetrahydrofuran, dimethylformamide, and dioxane.
  • DMSO dimethyl sulfoxide
  • DMSO dimethyl sulfoxide
  • amylose It is excellent and preferable.
  • DMSO dimethyl sulfoxide
  • 99: 1 to 70:30, preferably 95: 5 to 80 of water and dimethyl sulfoxide (DMSO) is used.
  • the solvent used in the present invention may contain various inorganic salts and low molecular organic compounds as long as they do not have an inhibitory effect on the formation of the inclusion complex between the host molecule and the guest molecule. Good.
  • the concentration at which the host molecule is dissolved in the solvent may be about 0.1 to 30% by weight, preferably about 0.1 to 5% by weight, more preferably about 0.3 to 3% by weight. If the concentration is too low, it is difficult to obtain clathrate precipitates, and productivity is poor and not economical. If the concentration is too high, the viscosity becomes high and handling becomes difficult. Also, even if the concentration is increased to a certain extent, productivity is not improved.
  • the concentration at which the guest substance is dissolved in the solvent may be about 0.1 to 30% by weight, preferably about 0.1 to 5% by weight, more preferably about 0.3 to 3% by weight. If the concentration is too low, it is difficult to obtain clathrate precipitates, and productivity is poor and not economical. If the concentration is too high, the viscosity becomes high and handling becomes difficult. Also, even if the concentration is increased to a certain extent, productivity is not improved.
  • the mixing ratio of the host molecule and the guest molecule dissolved in the solvent is such that the polymer guest molecule constituent unit is 1 unit or more, preferably 10 units or more per 6 units of the glucan host molecule constituent unit. Like that. If there are too few polymer guest molecule constituent units, the clathrate compound cannot be precipitated.
  • the mixing means is not particularly limited, but may be mixed by a method such as ultrasonic irradiation, a homogenizer, a propeller stirrer, a magnetic stirrer, a static mixer, or a combination thereof. Mixing by ultrasonic irradiation is preferred.
  • the temperature of the solution in the mixing step is 20 to 100 ° C, preferably 50 to 90 ° C. If the temperature is too high, the operation becomes extremely difficult. If the temperature is too low, the amylose has a strong herritus and no inclusion complex formation occurs. The longer the mixing time, the better, but it may be about 1 to 60 minutes, preferably about 5 to 30 minutes.
  • the mixed solution is mixed at the above temperature and time and then allowed to stand.
  • the standing condition may be about 1 to 24 hours under normal temperature and pressure.
  • the precipitate is centrifuged, The clathrate is recovered by a method such as filtration, and the precipitate is not dissolved, but may be purified by washing the precipitate with an appropriate solvent that dissolves only the guest polymer.
  • an inclusion compound is precipitated by adding a solvent such as ethanol or methanol to the mixture, and then the precipitate is The clathrate compound may be purified and collected by collecting and washing in the same manner as described above.
  • the force of obtaining an inclusion complex composed of an ⁇ -1,4 glucan host molecule partially modified with a hydroxyl group and a polymeric guest substance is characterized by the inclusion compound by X-ray diffraction. It can be confirmed from the spectrum obtained by NMR measurement that a typical peak has occurred.
  • a novel amylose-polymer inclusion complex and a method for producing the same were provided.
  • tetrahydrofuran (THF) lOmL was charged with 6-O-tritylamylose 0.60 g (l. 1 X 10 " 5 mol, 1.5 X 10 _3 mol / glucose unit) and the prescribed amount of NaH below.
  • 0.56 mL (9. OX 10 _3 mol) of yowi-methyl was added and stirred for 1 hour at room temperature. It was collected by filtration, washed with methanol, and dried under reduced pressure.
  • NaH-added amount (5.8 X 10 " 3 g, 2.4 X lO 'mol): When 8% methylation of the 2nd and 3rd hydroxyl groups NaH added amount (1.4 X 10— 2 g, 6.0 X lO 'mol): 20% methylation of hydroxyl groups at the 2nd and 3rd positions
  • the raw material amylose has a molecular weight of 21,360, and the methylation degree of the hydroxyl group at positions 2 and 3 is 3%.
  • This methylated amylose is expressed as MA2-3, and the molecular weight of amylose is 9,680, and the methylated amylose with 8% methylation at the 2- and 3-position hydroxyl groups is expressed as MA5-8.
  • MA2-3-MA2-100, MA5-8-MA5-50 were used as host polymers.
  • the guest polymer poly (tetramethylene oxide) (PTHF) and poly (force prolatatone) (PC L) were used.
  • FIG. 1 shows the 1 H-NMR ⁇ vector of the inclusion compound of MA2-8 and PTHF.
  • the 1 H-NMR ⁇ vector of the inclusion compound of MA5-20 and PTHF is shown in FIG.
  • the integral ratio of the 1-position proton (H) of the glucose unit in MA2-8 to the j8-position hydrogen proton (H) of PTHF is 5.0: 4.0. 1 unit of glucose H
  • ⁇ 2-8 includes PTHF1 unit with 5 glucose units.
  • Fig. 2 Force et al. 5-20 suggests that the PTHF1 unit is clathrated with 4.5 glucose units.
  • the integral ratio of the 1-position proton (H) of the glucose unit in MA2-8 to the ⁇ -position hydrogen proton ( ⁇ ⁇ ) of PCL is 7.1: 2.0.
  • 82-8 includes the PCL1 unit with a 7.1-course unit.
  • the obtained precipitate was placed on a glass substrate, and XRD measurement was performed at room temperature using RINT InPlane / ultraX18SAXS-IP manufactured by Rigaku.
  • Measurement conditions A slit having a scanning speed of 0.5 ° Zmin and a width of 0.3 mm was used.
  • FIG. 4 shows an XRD pattern diagram of PTHF-MA2-8 inclusion compound.
  • Figure 5 shows the XRD pattern of the PTHF-MA5-20 clathrate compound.
  • Figure 6 shows the XRD pattern of the PCL-MA2 8 clathrate compound.
  • 6-O trityl amylose 0. lg (l. 8 X 10 " 6 mol, 2.5 X 10 _4 mol / glucose unit) was dissolved in 2.5 mL of dehydrated dimethyl sulfoxide (DMSO).
  • DMSO dehydrated dimethyl sulfoxide
  • 2.5 mL of dehydrated pyridine and 40 mL of acetic anhydride were added, and the mixture was stirred at room temperature for 12 hours, 50 mL of methanol was added, and the precipitated pale yellow solid was collected by filtration, washed with methanol, and dried under reduced pressure.
  • R H or COCH 3
  • PTHF poly (tetramethylene oxide)
  • FIG. 7 shows the 1 H-NMR spectrum of the inclusion complex of 2,3-position acetylated amylose and PTHF.
  • R H or COCH 3
  • the obtained precipitate was placed on a glass substrate, and XRD measurement was performed at room temperature using RINT InPlane / ultraX18SAXS-IP manufactured by Rigaku.
  • Measurement conditions A slit having a scanning speed of 0.5 ° Zmin and a width of 0.3 mm was used.
  • FIG. 8 shows an XRD pattern diagram of the acetylated amylose PTHF inclusion complex.
  • DMSO dimethyl sulfoxide
  • the mixture was dialyzed against water for 3 days using a dialysis membrane having a molecular weight fraction of 3500. Thereafter, the product was obtained by freeze-drying.
  • carboxymethyl amylose having a carboxymethyl glycerol concentration of 3% was used.
  • R H or CH 2 C ⁇ OH
  • PTHF poly(tetramethylene oxide)
  • FIG. 9 shows the 1 H-NMR ⁇ vector of the inclusion complex of 2,3-position carboxymethylated amylose and PTHF.
  • R H or CH 2 COOH
  • the integral ratio of the 1-position proton ( ⁇ ) of the glucose unit in carboxymethylated amylose and the j8-position hydrogen proton ( ⁇ ) of PTHF is 3.4: 4.0.
  • the integral ratio suggests that carboxymethylated amylose clathrates PTHF1 units with 3.4 glucose units.
  • the obtained precipitate was placed on a glass substrate, and XRD measurement was performed at room temperature using RINT InPlane / ultraX18SAXS-IP manufactured by Rigaku.
  • Measurement conditions A slit having a scanning speed of 0.5 ° Zmin and a width of 0.3 mm was used.
  • Fig. 10 shows the XRD pattern of the carboxymethylated amylose PTHF inclusion complex.
  • a porous amylose ultra-thin film storing its three-dimensional structure precisely is obtained.
  • the hollow capsule formed from the ultrathin film of this amylose monopolymer inclusion complex can be used as a drug carrier that can control the release of the encapsulated drug by removing the guest polymer.
  • FIG. 1 1 H-NMR ⁇ vector diagram of inclusion compound of MA2-8 and PTHF.
  • FIG. 2 1 H-NMR ⁇ vector diagram of inclusion compound of MA5-20 and PTHF.
  • FIG. 3 1 H-NMR ⁇ vector diagram of inclusion compound of MA2-8 and PCL.
  • FIG. 4 is an XRD pattern diagram of PTHF—MA2 8 inclusion compound.
  • FIG. 5 XRD pattern diagram of PTHF-MA5-20 clathrate compound.
  • FIG. 6 XRD pattern diagram of PCL—MA2 8 inclusion compound.
  • FIG. 7 is a 1 H-NMR spectrum of an inclusion complex of 2,3-position acetylated amylose and PTHF.
  • FIG. 8 XRD pattern diagram of 2,3-position acetylated amylose PTHF inclusion complex.
  • FIG. 9 1 H-NMR spectrum of an inclusion complex of 2,3-position carboxymethylated amylose and PTHF.

Abstract

La présente invention concerne un composé d'insertion innovant produit par l'insertion directe d'une substance polymère dans l'intérieur creux d'une molécule d'amylose hôte. L'invention concerne plus spécifiquement un composé d'insertion produit à partir d'une molécule de α-1,4-glycane hôte dont un groupe hydroxyle est partiellement modifié et d'une substance polymère invitée. L'invention concerne également un procédé de production du composé d'insertion.
PCT/JP2006/317359 2005-09-02 2006-09-01 COMPOSÉ D'INSERTION AVEC POLYMÈRE INSÉRÉ DANS UN a-1,4-GLYCANE ET SON PROCÉDÉ DE PRODUCTION WO2007026883A1 (fr)

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Cited By (3)

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Publication number Priority date Publication date Assignee Title
JP2015086172A (ja) * 2013-10-31 2015-05-07 花王株式会社 化粧料組成物
JP2017509697A (ja) * 2014-02-27 2017-04-06 ビー‐オーガニック フィルムス コーポレイションＢ−Ｏｒｇａｎｉｃ Ｆｉｌｍｓ Ｃｏｒｐ． 一重らせんｖ構造を有する官能化デンプン中に含まれる生物活性剤
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Publication number Priority date Publication date Assignee Title
JP2015086172A (ja) * 2013-10-31 2015-05-07 花王株式会社 化粧料組成物
JP2017509697A (ja) * 2014-02-27 2017-04-06 ビー‐オーガニック フィルムス コーポレイションＢ−Ｏｒｇａｎｉｃ Ｆｉｌｍｓ Ｃｏｒｐ． 一重らせんｖ構造を有する官能化デンプン中に含まれる生物活性剤
JP2022541376A (ja) * 2019-06-14 2022-09-26 ニッケル， ゲアリー ビー． デンプン由来のクラスレート形成組成物
US11655491B2 (en) 2019-06-14 2023-05-23 Gary B. Nickel Starch-derived clathrate-forming compositions
JP7380996B2 (ja) 2019-06-14 2023-11-15 ニッケル， ゲアリー ビー． デンプン由来のクラスレート形成組成物
US11959114B2 (en) 2019-06-14 2024-04-16 Gary B. Nickel Starch-derived clathrate-forming compositions

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